Recent emphasis by the FDA as well as several high profile incidents have raised awareness as to the importance of the analysis of extractable and leachable compounds (E&L) from components employed in the storage or manufacture of biopharmaceuticals. The advent of single use bioprocess systems has introduced a new potential source for E&L’s as these systems are often comprised of polymeric materials. Several working groups (BPOG, BPSA), the FDA and USP have issued guidance on methodologies for performing E&L analyses for systems in contact with pharmaceuticals. These documents typically indicate that mass spectroscopy methods should be applied for discovery of E&L’s but provide little guidance as to the exact process which should be applied. In this presentation, we provide an example analysis on a single use bioprocess system and use this case study to demonstrate an LC/MS and GC/MS software workflow for analysis of E&L’s. This differential analysis workflow allows for the mining of both LC/MS and GC/MS data and providing a convenient way of visualizing the large volume of data arising from these experiments. We then compare the effects of the use of different standards applied for quantitation on the number of compounds which are considered toxicologically relevant. Suggestions regarding method design with an emphasis on optimum standard selection are also discussed.
